Expandable stent with sliding and locking radial elements

ABSTRACT

The present invention provides a lumen support stent with a clear through-lumen for use in a body lumen. The stent is formed from at least one series of sliding and locking radial elements and at least one ratcheting mechanism comprising an articulating element and a plurality of stops. The ratcheting mechanism permits one-way sliding of the radial elements from a collapsed diameter to an expanded diameter, but inhibits radial recoil from the expanded diameter.

RELATED APPLICATIONS

This is a divisional of U.S. patent application Ser. No. 10/452954,filed Jun. 3, 2003, which is a continuation of U.S. patent applicationSer. No. 09/739552, filed Dec. 14, 2000, now U.S. Pat. No. 6,623,521,which is a continuation-in-part of U.S. patent application Ser. No.09/283,800 filed on Apr. 1, 1999, now U.S. Pat. No. 6,224,626, which isa continuation-in-part of U.S. patent application Ser. No. 09/024,571filed on Feb. 17, 1998, now U.S. Pat. No. 6,033,436.

BACKGROUND OF THE INVENTION

This invention relates to expandable medical implants for maintainingsupport of a body lumen.

An important use of stents is found in situations where part of thevessel wall or stenotic plaque blocks or occludes fluid flow in thevessel. Often, a balloon catheter is utilized in a percutaneoustransluminal coronary angioplasty procedure to enlarge the occludedportion of the vessel. However, the dilation of the occlusion can causefissuring of atherosclerotic plaque and damage to the endothelium andunderlying smooth muscle cell layer, potentially leading to immediateproblems from flap formation or perforations in the vessel wall, as wellas long-term problems with restenosis of the dilated vessel.Implantation of stents can provide support for such problems and preventre-closure of the vessel or provide patch repair for a perforatedvessel. Further, the stent may overcome the tendency of diseased vesselwalls to collapse, thereby maintaining a more normal flow of bloodthrough that vessel.

Significant difficulties have been encountered with all prior artstents. Each has its percentage of thrombosis, restenosis and tissuein-growth, as well as various design-specific disadvantages.

Examples of prior developed stents have been described by Balcon et al.,“Recommendations on Stent Manufacture, Implantation and Utilization,”European Heart Journal (1997), vol. 18, pages 1536-1547, and Phillips,et al., “The Stenter's Notebook,” Physician's Press (1998), Birmingham,Mich. The first stent used clinically was the self-expanding “Wallstent”which comprised a metallic mesh in the form of a Chinese fingercuff.This design concept serves as the basis for many stents used today.These stents were cut from elongated tubes of wire braid and,accordingly, had the disadvantage that metal prongs from the cuttingprocess remained at the longitudinal ends thereof. A second disadvantageis the inherent rigidity of the cobalt based alloy with a platinum coreused to form the stent, which together with the terminal prongs, makesnavigation of the blood vessels to the locus of the lesion difficult aswell as risky from the standpoint of injury to healthy tissue along thepassage to the target vessel. Another disadvantage is that thecontinuous stresses from blood flow and cardiac muscle activity createsignificant risks of thrombosis and damage to the vessel walls adjacentto the lesion, leading to restenosis. A major disadvantage of thesetypes of stents is that their radial expansion is associated withsignificant shortening in their length, resulting in unpredictablelongitudinal coverage when fully deployed.

Among subsequent designs, some of the most popular have been thePalmaz-Schatz slotted tube stents. Originally, the Palmaz-Schatz stentsconsisted of slotted stainless steel tubes comprising separate segmentsconnected with articulations. Later designs incorporated spiralarticulation for improved flexibility. These stents are delivered to theaffected area by means of a balloon catheter, and are then expanded tothe proper size. The disadvantage of the Palmaz-Schatz designs andsimilar variations is that they exhibit moderate longitudinal shorteningupon expansion, with some decrease in diameter, or recoil, afterdeployment. Furthermore, the expanded metal mesh is associated withrelatively jagged terminal prongs, which increase the risk of thrombosisand/or restenosis. This design is considered current state of the art,even though their thickness is 0.004 to 0.006 inches.

Another type of stent involves a tube formed of a single strand oftantalum wire, wound in a sinusoidal helix; these are known as coilstents. They exhibit increased flexibility compared to the Palmaz-Schatzstents. However, they have the disadvantage of not providing sufficientscaffolding support for many applications, including calcified or bulkyvascular lesions. Further, the coil stents also exhibit recoil afterradial expansion.

One stent design described by Fordenbacher, employs a plurality ofelongated parallel stent components, each having a longitudinal backbonewith a plurality of opposing circumferential elements or fingers. Thecircumferential elements from one stent component weave into pairedslots in the longitudinal backbone of an adjacent stent component. Byincorporating locking means within the slotted articulation, theFordenbacher stent may minimize recoil after radial expansion. Inaddition, sufficient numbers of circumferential elements in theFordenbacher stent may provide adequate scaffolding. Unfortunately, thefree ends of the circumferential elements, protruding through the pairedslots, may pose significant risks of thrombosis and/or restenosis.Moreover, this stent design would tend to be rather inflexible as aresult of the plurality of longitudinal backbones.

Some stents employ “jelly roll” designs, wherein a sheet is rolled uponitself with a high degree of overlap in the collapsed state and adecreasing overlap as the stent unrolls to an expanded state. Examplesof such designs are described in U.S. Pat. Nos. 5,421,955 to Lau, U.S.Pat. Nos. 5,441,515 and 5,618,299 to Khosravi, and U.S. Pat. No.5,443,500 to Sigwart. The disadvantage of these designs is that theytend to exhibit very poor longitudinal flexibility. In a modified designthat exhibits improved longitudinal flexibility, multiple short rollsare coupled longitudinally. See e.g., U.S. Pat. No. 5,649,977 toCampbell and U.S. Pat. Nos. 5,643,314 and 5,735,872 to Carpenter.However, these coupled rolls lack vessel support between adjacent rolls.

Another form of metal stent is a heat expandable device using Nitinol ora tin-coated, heat expandable coil. This type of stent is delivered tothe affected area on a catheter capable of receiving heated fluids. Onceproperly situated, heated saline is passed through the portion of thecatheter on which the stent is located, causing the stent to expand. Thedisadvantages associated with this stent design are numerous.Difficulties that have been encountered with this device includedifficulty in obtaining reliable expansion, and difficulties inmaintaining the stent in its expanded state.

Self-expanding stents are also available. These are delivered whilerestrained within a sleeve (or other restraining mechanism), that whenremoved allows the stent to expand. Self-expanding stents areproblematic in that exact sizing, within 0.1 to 0.2 mm expandeddiameter, is necessary to adequately reduce restenosis. However,self-expanding stents are currently available only in 0.5 mm increments.Thus, greater selection and adaptability in expanded size is needed.

In summary, there remains a need for an improved stent: one that hassmoother marginal edges, to minimize restenosis; one that is smallenough and flexible enough when collapsed to permit uncomplicateddelivery to the affected area; one that is sufficiently flexible upondeployment to conform to the shape of the affected body lumen; one thatexpands uniformly to a desired diameter, without change in length; onethat maintains the expanded size, without significant recoil; one thathas sufficient scaffolding to provide a clear through-lumen; one thatemploys a thinner-walled design, which can be made smaller and moreflexible to reach smaller diameter vessels; and one that has athinner-walled design to permit faster endothelialization or covering ofthe stent with vessel lining, which in turn minimizes the risk ofthrombosis from exposed stent materials.

SUMMARY OF THE INVENTION

The present invention relates to an expandable intraluminal stent,comprising a tubular member with a clear through-lumen. The tubularmember has proximal and distal ends and a longitudinal length definedtherebetween, and a circumference, and a diameter which is adjustablebetween at least a first collapsed diameter and at least a secondexpanded diameter. In a preferred mode, the longitudinal length remainssubstantially unchanged when the tubular member is adjusted between thefirst collapsed diameter and the second expanded diameter. The tubularmember includes at least one module comprising a series of sliding andlocking radial elements, wherein each radial element defines a portionof the circumference of the tubular member and wherein no radial elementoverlaps with itself in either the first collapsed diameter or thesecond expanded diameter.

In one aspect, each radial element may comprise at least one elongatedrib disposed between first and second end portions. Preferably, theradial elements that comprise a module alternate between radial elementshaving an odd number of elongated ribs and radial elements having aneven number of elongated ribs. In one preferred mode, the radialelements alternate between radial elements having one elongated rib andradial elements having two elongated ribs.

The stent also includes at least one articulating mechanism comprising atab and at least one stop. The articulating mechanism permits one-waysliding of the radial elements from the first collapsed diameter to thesecond expanded diameter, but inhibits radial recoil from the secondexpanded diameter.

In variations to the stent, the tubular member may comprise at least twomodules which are coupled to one another by at least one linkageelement. In one variation, the tubular member may further comprise aframe element that surrounds at least one radial element in each module.In stents in which the tubular member comprises at least two modules,such frame elements from adjacent modules may be coupled. The couplingmay include a linkage element extending between the frame elements. Inaddition or in the alternative, the frame elements from adjacent modulesmay be coupled by interlinking of the frame elements. In another aspect,the intermodular coupling may be degradable allowing for the independentmodules to adapt to the vessel curvature.

In another variation to the stent of the present invention, any amountof overlap among the radial elements within in a module remains constantas the tubular member is adjusted from the first collapsed diameter tothe second expanded diameter. This amount of overlap is preferably lessthan about 15%.

The radial recoil of the tubular member in accordance with one preferredembodiment is less than about 5%. The stiffness of the stent ispreferably less than about 0.1 Newtons force/millimeter deflection. Thetubular member also preferably provides a surface area coverage ofgreater than about 20%.

In accordance with another variation of the present stent, the tubularmember is at least partially radiopaque. The radial elements may be madesubstantially from a material which is work hardened to between about80% and 95%. In one preferred variation, the radial elements in theexpandable intraluminal stent are made from a material selected from thegroup consisting of a polymer, a metal, a ceramic, and combinationsthereof. In one mode, the material may be degradable.

In another mode of the invention, the material may also include abioactive agent. The material is preferable adapted to deliver an amountof the bioactive agent which is sufficient to inhibit restenosis at thesite of stent deployment. In one variation, the radial elements areadapted to release the bioactive agent during stent deployment when thetubular member is adjusted from the first collapsed diameter to thesecond expanded diameter. The bioactive agent(s) is preferably selectedfrom the group consisting of antiplatelet agents, antithrombin agents,antiproliferative agents, and antiinflammatory agents.

In another variation, the tubular member further comprises a sheath,such as for example in a vessel graft.

In one aspect, the expandable intraluminal stent comprises at least twomodules, wherein the expanded diameters of the first and second modulesare different.

The articulating mechanism(s) of the present invention which allow thestent to expand but inhibit stent recoil, may comprise a slot and a tabon one radial element and at least one stop on an adjacent radialelement which is slideably engaged in the slot, wherein the tab isadapted to engage the at least one stop. The articulating mechanism(s)may also include an expansion resistor on the slideably engaged radialelement, wherein the expansion resistor resists passing through the slotduring expansion until further force is applied, such that the radialelements in the module expand in a substantially uniform manner. Inanother variation, the articulating mechanism may include a release,such that actuation of the release permits sliding of the radialelements from the second expanded diameter back to the first collapseddiameter for possible removal of the stent. In another variation, thestent may comprise a floating coupling element having an articulatingmechanism.

In another variation, the expandable intraluminal stent comprises atubular member with a clear through-lumen and a diameter which isadjustable between at least a first collapsed diameter and at least asecond expanded diameter. The tubular member comprises a series ofsliding and locking radial elements made from a degradable material,wherein each radial element in the series defines a portion of thecircumference of the tubular member and wherein no radial elementoverlaps itself. This stent also has at least one articulating mechanismthat permits one-way sliding of the radial elements from the firstcollapsed diameter to the second expanded diameter, but inhibits radialrecoil from the second expanded diameter. The degradable material may beselected from the group consisting of polyarylates (L-tyrosine-derived),free acid polyarylates, polycarbonates (L-tyrosine-derived),poly(ester-amides), poly(propylene fumarate-co-ethylene glycol)copolymer, polyanhydride esters, polyanhydrides, polyorthoesters, andsilk-elastin polymers, calcium phosphate, magnesium alloys or blendsthereof.

In a variation to the degradable stent, the degradable polymer mayfurther comprise at least one bioactive agent, which is released as thematerial degrades. The at least one bioactive agent may be selected fromthe group consisting of antiplatelet agents, antithrombin agents,antiproliferative agents and antiinflammatory agents.

In another variation, the stent material may be fiber-reinforced. Thereinforcing material may be a degradable material such as calciumphosphate (e.g., BIOGLASS). Alternatively, the fibers may be fiberglass,graphite, or other non-degradable material.

In another mode, the stent of the present invention comprises a tubularmember having a wall and a clear through-lumen. The tubular membercomprises a series of sliding and locking radial elements which do notoverlap with themselves. The radial elements further comprise aratcheting mechanism that permits one-way sliding of the radial elementsfrom a first collapsed diameter to a second expanded diameter. Thetubular member in this embodiment has a stiffness of less than about 0.1Newtons force/millimeter deflection, and the wall of the tubular memberhas a thickness of less than about 0.005 inches.

BRIEF DESCRIPTION OF THE DRAWINGS

FIGS. 1A-C are plan views of one module of an expandable stent inaccordance with the present invention, illustrating a series of radialelements. The assembled module is shown in various states, from acollapsed state (FIG. 1A), to a partially expanded state (FIG. 1B), toan expanded state (FIG. 1C).

FIGS. 2A and 2B are schematic views of the individual radial elementsfrom FIGS. 1A-C. A one-rib radial element is shown in FIG. 2A and atwo-rib radial element is shown in FIG. 2B.

FIG. 3 is a perspective view of a tubular member formed from one modulecomprising a series of one-rib and two-rib sliding and locking radialelements.

FIGS. 4A and 4B are plan views of another embodiment of a module havinga floating coupling element, wherein the one-rib radial elements furthercomprise a frame element. The module is shown in a collapsed state (FIG.4A) and an expanded state (FIG. 4B).

FIG. 4C is a perspective view of a tubular member comprising a pluralityof modules shown in FIGS. 4A and 4B.

FIG. 4D is a perspective view of a tubular member comprising a pluralityof the modules shown in FIGS. 4A and 4B, wherein the expanded diameterof adjacent modules is not the same.

FIG. 5 is a plan view of another embodiment of a module comprisingsliding and locking radial elements having two ribs each and a frameelement.

FIG. 6 is a plan view of a variation of the stent showing the linkage ofadjacent modules, each comprising alternating one-rib and a two-ribradial elements, wherein the one-rib elements have a frame elementadapted to facilitate linkage of adjacent modules in the circumferentialaxis.

FIG. 7 is a plan view of a variation of the stent showing intermodulecoupling through inter-linking of adjacent frame elements.

FIG. 8 is a plan view of a variation of the stent showing intermodulecoupling through direct attachment of adjacent frame elements to oneanother.

FIG. 9 is a perspective view of a tubular member comprising one modulein accordance with one aspect of the present invention.

FIG. 10 is a perspective view of a tubular member comprising a pluralityof modules.

FIG. 11 is a plan view of a snap-together variation of the moduledesign, having a floating coupling element and frame elements on theone-rib radial elements.

FIGS. 12A-C are perspective views showing the steps in forming a biasedor chamfered stop.

FIGS. 13A and 13B show a releasable articulating mechanism in accordancewith a collapsible variation of the present stent. An exploded view ofthe components of the releasable articulating mechanism is shown in FIG.13A. A perspective view of several releasable articulating mechanismspositioned on a module are shown in FIG. 13B.

FIGS. 14A and 14B show comparative longitudinal flexibility data forundeployed mounted (collapsed diameter) stents (FIG. 14A) and fordeployed (expanded diameter) stents (FIG. 14B).

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT

Stent Design

The present invention relates to a radially expandable stent used toopen, or to expand a targeted area in a body lumen. In one preferredembodiment of the present invention, the assembled stent comprises atubular member having a length in the longitudinal axis and a diameterin the radial axis, of appropriate size to be inserted into the bodylumen. The length and diameter of the tubular member may varyconsiderably for deployment in different selected target lumensdepending on the number and configuration of the structural components,described below. The tubular member is adjustable from at least a firstcollapsed diameter to at least a second expanded diameter. One or morestops and engaging elements or tabs are incorporated into the structuralcomponents of the tubular member whereby recoil (i.e., collapse from anexpanded diameter to a more collapsed diameter) is minimized to lessthan about 5%.

The tubular member in accordance with the present invention has a “clearthrough-lumen,” which is defined as having no structural elementsprotruding into the lumen in either the collapsed or expanded diameters.Further, the tubular member has smooth marginal edges to minimize thetrauma of edge effects. The tubular member is preferably thin-walled(wall thickness depending on the selected materials ranging from lessthan about 0.006 inches for plastic and degradable materials to lessthan about 0.002 inches for metal materials) and flexible to facilitatedelivery to small vessels and through tortuous vasculature. The thinwalled design will also minimize blood turbulence and thus risk ofthrombosis. The thin profile of the deployed tubular member inaccordance with the present invention also facilitates more rapidendothelialization of the stent.

The wall of the tubular member comprises at least one module, whichconsists of a series of sliding and locking radial elements. Preferably,a plurality of modules are connected in the longitudinal axis vialinkage elements which couple at least some of the radial elementsbetween adjacent modules. The radial elements are configured within eachmodule so as to define the circumference of the tubular member. Eachradial element within a module is preferably a discrete, unitarystructure, comprising one or more circumferential ribs bowed in theradial axis to form a fraction of the total circumference of the tubularmember. The radial elements within a module are preferably assembled sothat all of the circumferential ribs are substantially parallel to oneanother. At least one of the ribs in each radial element has one or morestops disposed along the length of the rib. At least some of the radialelements also have at least one articulating mechanism for slideablyengaging the rib(s) from adjacent, circumferentially offset radialelements. In one aspect of the present invention, the articulatingmechanism includes a tab for engaging the stops disposed along theslideably engaged adjacent rib. The articulation between the tab fromone radial element and the stops from an adjacent radial element is suchthat a locking or ratcheting mechanism is formed, whereby the adjacentradial elements may slide circumferentially apart from one another, butare substantially prevented from sliding circumferentially toward oneanother. Accordingly, the tubular member may be radially expanded from asmaller diameter to a larger diameter, but recoil to a smaller diameteris minimized by the locking mechanism. The amount of recoil can becustomized for the application by adjusting the size and the spacingbetween the stops along the ribs. Preferably, the recoil is less thanabout 5%.

Some aspects of the present stents are disclosed in U.S. Pat. No.6,033,436 issued to Steinke, and co-pending U.S. application Ser. No.09/283,800. The disclosures of which are hereby incorporated in theirentirety by reference thereto.

Referring to FIG. 1A-C, a plan view of one module 10 is illustratedcomprising a series of sliding and locking radial elements 20 inaccordance with one embodiment of the present invention. The picturedmodule is shown in a two-dimensional, flat plane. Each radial elementhas one or more elongated ribs 22 (in the vertical axis) with agenerally perpendicular end portion 24 (in the horizontal axis),permanently affixed to each end of each rib. Each rib has at least onestop 30. The radial elements in the module alternate from a one-ribconfiguration 20′ to a two-rib configuration 20″. The illustratedone-rib configuration 20′ has a single rib 22 with a plurality of stops30, whereas the illustrated two-rib configuration 20″ has two ribs, eachwith a plurality of stops 30. The radial elements in accordance with theinvention could have different numbers of circumferential ribs 22,however, vertically adjacent radial elements preferably alternatebetween an odd-numbered rib configuration and an even-numbered ribconfiguration, as illustrated in FIGS. 1A-C.

The odd-even alternation in adjacent radial elements facilitates nestingof the circumferential ribs 22 within a module, while maintaining aconstant width (w). However, if the radial elements are configureddifferently, e.g., in a parallelogram shape as opposed to a rectangularshape, wherein the ribs exhibit a non-circumferential orientation, thenchanges in the longitudinal length of the module would be expected uponexpansion of the tubular member. Such variations are encompassed withinthe present invention.

With reference to FIGS. 1A-C, some of the end portions 24 of the radialelements 20 in the illustrated design are depicted with articulatingmechanisms 34 each comprising a slot 36 for slidably engaging a rib froma vertically adjacent radial element and a tab 32 for engaging the stops30 in the slidably engaged rib. The end portions 24 of the one-ribradial elements 20′ are generally adapted to articulate with each rib 22from the slideably engaged, vertically adjacent two-rib radial element20″. The end portions 24 of the two-rib radial elements 20″ aregenerally adapted to articulate with the single rib 22 of the slideablyengaged, vertically adjacent one-rib radial element 20′. Thearticulating mechanism is shown in greater detail in FIGS. 2A and 2B.The stops 30 may be evenly distributed along the entire length (as shownon the second radial element from the bottom), or the stops may bedistributed unevenly along the ribs (as shown in the upper most radialelement).

The articulation between the tab 32 from one radial element and thestops 30 from an adjacent radial element creates a locking or ratchetingmechanism, such that only one-way sliding (expansion) can take place.Accordingly, the series of radial elements in plan view, as shown inFIGS. 1A-C, is adjustable from a collapsed state, as shown in FIG. 1A,to a partially expanded state, as shown in FIG. 1B, to a fully expandedstate, as shown in FIG. 1C. Expansion of the module 10 in plan view maybe accomplished by application of opposing forces (arrows). The nested,sliding and locking radial elements 20 slide apart from one another,thereby increasing the height (h) of the series in the vertical axis,with no change in the width (w) of the series in the horizontal axis.The locking mechanism formed by the articulation between the tab 32 andthe individual stops 30 prevents the expanded series from recoiling backto a more collapsed height.

When the module 10 is rolled to form a tubular member, a slideablearticulation may be made between the end portion on the radial elementon top of the module and the rib from the radial element on the bottomof the module. Likewise, a slideable articulation may also be madebetween the end portion on the radial element on the bottom of themodule and the two ribs from the radial element on top of the module. Ina variation, after rolling to form a tubular member, the top and bottomend portions can be connected to one another by a variety of fasteningmeans known in the art, including welding, adhesive bonding, mechanicalor snap fit mechanism, etc. In other modes, specialized structuralelements may be included to facilitate coupling of the top and bottomportions of the rolled module. Examples, of specialized circumferentialcoupling elements are detailed below with reference to FIGS. 4A and 4B.

With reference to FIGS. 2A and 2B, individual one-rib 20′ and two-rib20″ radial elements, respectively, are shown unassembled in greaterdetail. Both the one-rib radial element 20′ in FIG. 2A and the two-rib20″ radial element in FIG. 2B have at least one circumferential rib 22and an end portion 24 on each end of the rib. The rib has one or morestops 30 disposed along the length of the rib 22. One end of each of theillustrated radial elements includes an articulating mechanism 34comprising a tab 32 and a slot 36. Also illustrated in FIGS. 2A and 2Bare linkage elements 40, which extend laterally from an end portion 24of a radial element. These linkage elements 40 are used to couple radialelements between adjacent modules. The linkage elements may extend fromeither or both end portions 24 of either the one-rib 20′ or two-rib 20″radial elements. In one preferred mode (as illustrated), the linkageelements 40 extend off of both end portions 24 of a one-rib radialelement 20′. The configuration and angle of the linkage elements mayvary substantially depending on the desired linkage distance betweenmodules and the desired flexibility and surface area coverage of thestent.

A tubular member formed from a single module 10 comprising four one-ribradial elements 20′ and four two-rib radial elements 20″, similar to theplan view described with reference to FIGS. 1A-D and FIGS. 2A-B, isshown in FIG. 3. The radial elements that form the wall of the tubularmember alternate between radial elements having odd and even-numbers ofcircumferential ribs 22. Each rib in the illustrated module has one ormore stops 30. An articulating mechanism (shown in greater detail inFIGS. 2A and 2B), has a tab 32 that engages the stops and prevents thetubular member from collapsing to a smaller diameter. Each radialelement forms a portion of the total circumference of the tubular member(in this case ⅛ of the circumference). Preferably, the total number ofradial elements that comprise a module varies between about 2 and 12.More preferably, the number of radial elements is between 4 and 8 radialelements. Linkage elements 40 are shown extending laterally away fromthe module on both sides. The linkage elements 40 are for coupling themodule to similar modules to create a tubular member with a greaterlongitudinal length.

A variation of the basic module design described above with reference toFIGS. 1A-D and FIGS. 2A-B is shown in FIGS. 4A and 4B. The module isillustrated in plan view in both a collapsed state (FIG. 4A) and anexpanded state (FIG. 4B). In this variation of the stent, similar to theearlier design, a module 110 comprises a series of sliding and lockingradial elements 120. Each radial element has one or more elongated ribs122 (in the vertical axis) with a substantially perpendicular endportion 124 (in the horizontal axis), permanently affixed to each end ofeach rib. Each rib has one or more stops 130. The radial elements in themodule alternate from a one-rib configuration 120′ to a two-ribconfiguration 120″. The one-rib configuration 120′ has a single rib 122with one or more stops 130, whereas the two-rib configuration 120″ hastwo ribs, each with one or more stops 130.

Like the previously described module, the odd-even alternation inadjacent radial elements facilitates nesting of the circumferential ribs122 within a module, while maintaining a constant width (w). Some of theend portions 124 of the radial elements 120 in the illustrated designare depicted with articulating mechanisms 134 each comprising a slot 136for slidably engaging a rib from a vertically adjacent radial elementand a tab 132 for engaging the stops 130 in the slidably engaged rib.The feathered edges 138 of the articulating mechanisms 134 shown inFIGS. 4A and 4B indicate where the articulating mechanism has beenwelded onto the end portions 124 of the respective radial elements,thereby creating the slot 136 through which the engaged rib can slide.The end portions 124 of the one-rib radial elements 120′ are generallyadapted to articulate with each rib 122 from the slideably engaged,vertically adjacent two-rib radial element 120″. The end portions 124 ofthe two-rib radial elements 120″ are generally adapted to articulatewith the single rib 122 of the slideably engaged, vertically adjacentone-rib radial element 120′. The stops 130 may be evenly distributedalong the entire length (as shown), or the stops may be distributedunevenly along the ribs, or there may be only a single stop.

In FIG. 4A and 4B, a bump 161 is also shown on the one-rib radialelements 120″. These bumps can be incorporated along the length of therib(s) in order to provide a temporary stop. During expansion, the ribwith the bump 161 temporarily stops sliding when the bump 161 enters theslot 136 of the articulating mechanism 138. This temporary stop allowsother elements to fully expand before the temporary stop is overcome byadditional radial expansion force. The incorporation of one or more ofthese bumps in a module facilitates uniform expansion of the radialelements within the module. In addition or in the alternative to thetemporary stop created by the bump 161, some elements may have only onestop so that this element is expanded first to the stop, with the otherelements having multiple stops providing preferred expansion steps.

The articulation between the tab 132 from one radial element and thestops 130 from an adjacent radial element creates a locking orratcheting mechanism, such that only one-way sliding (expansion) cantake place. The nested, sliding and locking radial elements 120 slideapart from one another, thereby increasing the height of the series inthe vertical axis, with no change in the width of the series in thehorizontal axis. The locking mechanism formed by the articulationbetween the tab 132 and the individual stop(s) 130 prevents the expandedseries from recoiling back to a more collapsed height.

The module 110 shown in FIGS. 4A and 4B includes a floating couplingelement 150 which is shaped like the end portion 124 of a two-rib radialelement 120″, having one articulating mechanism 134 adapted to slideablyengage the circumferential rib 122 of a one-rib radial element 120′. Invariations to the depicted embodiment, the floating coupling element maybe adapted to float over more than one rib in radial elements having twoor more circumferential ribs. The coupling element 150 is also adaptedto couple with the end portion 124 of the top radial element 121 in theseries. Both the coupling element 150 and the end portion 124 on the topradial element 121 are configured so as to have coupling arms 152 and154, and 152′ and 154′, which may exhibit a complimentary configurationas illustrated.

Another specialization illustrated in FIGS. 4A and 4B, are frameelements 160 from which linkage elements 140 extend laterally away fromthe frame elements 160. In the module depicted in FIGS. 4A and 4B, theframe elements 160 are only employed on the one-rib radial elements120′. The frame elements are shown attached to and extending between theend portions 124 of the one-rib radial elements 120′, so that thecircumferential rib 122 is surrounded, or framed, by the end portions124 and frame elements 160. The use of frame elements to facilitatecoupling between adjacent modules has several advantages. The frameelements contribute additional physical support to the vessel wall.Larger surface area of the individual elements may be desirable in someinstances, first to provide greater support for the surrounding lumen,and second the larger surface area provides a larger carrier forsite-directed introduction of biologically active agents (discussedbelow). Alternatively, a smaller surface can be configured to minimizeimpact of the stent material on the vessel wall, for example, by usingnarrower ribs and frame elements. By suspending the linkage elements 140laterally outward from the radial elements, the frame elements minimizethe length of the linkage elements 140 that will be necessary to coupleadjacent modules, while separating the sliding ribs from one module fromthose of the adjacent module. Coupling of the linkage elements 140 inadjacent modules provides for a very flexible stent. The flexure is alsocarried to the frame element 160, allowing much larger movement, andthus, increased flexibility. In variations to this mode, the frameelements can be employed in radial elements have more than one rib. Seee.g., FIG. 5, showing a module design comprising a series of two-ribradial elements, each having frame elements.

With reference to FIG. 5, a variation of odd-even radial elements isshown, wherein each of the two illustrated radial elements 220 have twocircumferential ribs 222 and two articulating mechanisms 234 disposed onat least one of the end portions 224 of the radial elements andcomprising a tab 232 and a slot 236. As in previous modes of the presentinvention, the circumferential ribs may have a plurality of stops 230disposed along the length of the rib. Each of the radial elements has aframe element 260, which is substantially rectangular in shape (linkageelements are not shown). The frame element may be any shape consistentwith the function of surrounding the ribs and providing a connectionpoint for coupling the radial elements from one module to those from anadjacent module. Preferably the frame elements permit nesting of theribs in both collapsed and expanded states, without overlapping stentcomponents, which would increase the thickness of the stent.

The shape of the frame elements can be varied to cause circumferentialoff-setting of the different radial elements having odd and even-numbersof ribs. For example, with reference to FIG. 6, the lateral coupling ofone pair of radial elements (a one-rib 320′ and a two-rib 320″ radialelement) from one module are connected by the linkage element 340 toanother pair of radial elements from an adjacent module. The frameelements 360 are shown in this embodiment surrounding only the one-ribradial elements 320′. The frame elements 360 are configured so as topromote nesting (and not overlap) of ribs 322 and frame elements 360,minimize the lateral space between the modules, and facilitate linkageby a circumferentially, rather than longitudinally, oriented linkageelement 340, thereby maximizing the circumferential scaffolding andradial support.

With reference to FIG. 7, there is illustrated a variation in thecoupling mechanism between adjacent modules. No separate linkingelements are employed. Instead, the frame elements 360 from adjacentmodules may be assembled by weaving so as to inter-link with one anotheras shown. This coupling between adjacent modules allows much greaterstent flexibility.

With reference to FIG. 8, there is illustrated another variation in thecoupling mechanism between adjacent modules. No separate linkingelements are employed. Instead, the frame elements 360 from adjacentmodules are directly joined to one another as shown. The frame elementsfrom adjacent modules may attached by any means suitable for thematerial, e.g., welding, etc. In one embodiment, frame elements fromadjacent modules may be constructed (e.g., cut out) from a single pieceof material. This direct coupling of frame elements from adjacentmodules tends to produce a stent with greater axial strength.

A variety of different articulating mechanisms and stops are encompassedwithin the present invention; including but not limited to the slot andtab designs disclosed herein and illustrated in FIGS. 1-8, as well asthose disclosed in the parent case, now U.S. Pat. No. 6,033,436 toSteinke, which is incorporated herein in its entirety by referencethereto.

It will be appreciated by those skilled in the art that the basic moduledesign of a series of sliding and locking radial elements provides themanufacturer with a great deal of flexibility with regard to thecollapsed and expanded diameters of the stent as well as thelongitudinal length. Increased expanded diameter and expansion ratio canbe achieved by increasing the number of radial elements within eachmodule. Increased longitudinal length can be achieved by increasing thenumber of modules that are linked to form the tubular member (from onemodule as shown in FIG. 9 to six modules as shown in FIG. 10).

With reference to FIG. 9, a tubular member having only one module 410comprising a series of four radial elements (two one-rib radial elements420′ and two two-rib radial elements 420″). In the pictured module 410,no specialized coupling element, like the floating coupling elementdescribed with respect to FIGS. 4A and 4B is employed, although such acoupling element could be used in this module without departing from thebasic design. The illustrated frame elements 460 have a rectangularshape and surround only the one-rib radial elements 420′. The moduleshown in FIG. 9 is in an expanded state and is subject to only minimumrecoil or collapse (<about 5%) because of the ratcheting effect createdby the articulation between a tab 432 on the articulating mechanism 434of one radial element and a stop 430 on the slideably engaged rib 422from the adjacent radial element. The articulating mechanism is shown asa separate structural element that has been affixed, e.g., by welding,to the end portion 424 of the respective radial element, therebyentrapping and slideably engaging the rib(s) from the adjacent radialelement.

In FIG. 10, a stent in accordance with the present invention is shown,comprising a tubular member 500 having six modules 510 which are linkedin the longitudinal axis (for clarity, linkage elements extendingbetween the frame elements in adjacent modules are not shown).

In another variation of the present invention, a series of radialelements are illustrated in FIG. 11, wherein the articulating mechanismis formed by a tab 632 in a one-way locking slot 633. This designeliminates the need to attach an overlapping articulating mechanism,e.g., by welding, to entrap and slideably engage a circumferential ribfrom an adjacent radial element. As shown in FIG. 11, an entry slot 631is provided at one end of the central locking slot 633, which isdisposed along at least a portion of the length of each rib in eachradial element. The entry slot 631 is adapted to permit a tab 632 on theend portion 624 of one radial element 620 to fit into and engage thelocking slot 633 in the rib. Once the tab(s) 632 is placed through theentry slot(s) 631 the radial elements 620 can be slid apart enough toprevent the tab 632 from coming back out of the entry slot 631. Thelocking slot 633 is adapted to allow the tab to slide through the slotin only one direction (to a more expanded configuration). For example,as illustrated, the locking slot 633 has a series of serrated notches orstops 630, which are offset on both sides of the slot and which permitthe tab 632 to move through the slot 633 in one direction, but which areshaped so as to engage the tab and prevent it from moving through theslot in the opposite direction, i.e., prevent collapse of the expandedstent. Any of a variety of locking slot and stop configurations areencompassed within this snap-together design. Some alternative lockingslot and stop configurations are disclosed in the parent application,now U.S. Pat. No. 6,033,436 to Steinke.

The weldless design module illustrated in FIG. 11 is shown with framingelements 660 with linkage elements 640 around the one-rib radialelements and a floating coupling element 650 with coupling arms 652 and654 for mating with complementary coupling arms 652′ and 654′ on the endportion 624 of the top radial element in the series. Because theintermodule coupling can be made to the frame elements this increasedlength allows the stent to be very flexible both in the collapsed andexpanded states.

Another variation of the present invention includes varying thearticulating mechanism and rib configurations so as to produceincreasing friction with progressive expansion. This variation mayfacilitate uniform expansion of all radial elements within a module.

In another variation of the present stent, different modules within thestent may exhibit different expanded diameters, such that the stent maybe adjustable to different luminal states along the length of the stent.Accordingly, the stent may exhibit a tapered configuration in itsdeployed state, having a larger diameter at one end with progressive orstep-wise decreases in modular expanded diameter moving toward the otherend of the stent.

It will be appreciated by those of skill in the art that theinterlocking and sliding radial element design of the present inventionprovides the manufacturer with substantial flexibility in customizingthe stent for different applications. Because overlap of stentcomponents is minimized by the nesting of ribs and frame elements, thecollapsed profile can be very thin without compromising radial strength.Moreover, the degree of overlap does not change substantially duringexpansion, unlike jelly-roll designs which expand by unraveling of arolled sheet. Furthermore, the deployment flexibility of the presentstent can be customized by changing the length, configuration and numberof lateral linkage elements employed. Thus, a very flexible andultra-thin embodiment of the present stent is deemed to be uniquelysuited for deployment in small and difficult to reach vessels, such asthe intercranial vessels distal to the carotids and the remote coronaryvessels.

In another variation, the stent may be used in combination with acovering or sheath to provide a vessel graft, for example, in thetreatment of an aneurysm. Materials and methods of making vessel grafts(stent and sheath) incorporating the present stent design are describedin detail below.

In another variation of the present invention, the stops that aredisposed along an elongate rib may be shaped so as to facilitate lockingof the tab from the articulating member within the stop, wherein theshape of the hole is adapted to provide a channel which will have a biasfor capturing parts (i.e., a tab) sliding past it. With reference toFIGS. 12A-C, there are illustrated the steps in forming one embodimentof such a stop. In FIG. 12A, the stent component 700 can be etched fromthe top 700′ and bottom 700″ surfaces. The top and bottom surfaces arecoated or masked in some areas 702′ and 702″, respectively, with a layerthat resists etching (e.g., by chemical, laser, etc.), leaving uncoatedareas 704′ and 704″ on the top and bottom, respectively, susceptible toetching. The uncoated areas are offset by a distance 706, which allowssome overlap 708 between the top and bottom uncoated areas 704′ and704″. As illustrated in FIG. 12B, during the etching process whereinstent material is removed, the uncoated areas 704′ and 704″ becomecavities 710 extending through the stent material. At some point duringthe etching process, as shown in FIG. 12C, the cavities meet in theoverlap area 708 and create a through hole or channel 712. The stop thusformed has a chamfered edge that is biased for capturing a tab as itslides over the stop.

In another embodiment of the present stent, the locking mechanism may bedesigned to be releasable, wherein the stent may be collapsed forremoval from the body lumen. Whereas the other configurations in thisdisclosure are designed for permanent locking of the members in theexpanded state, there may be a need for a reversible, or unlockingmechanism. The components of one possible release mechanism areillustrated in exploded view in FIG. 13A. Most aspects of the stent inaccordance with the present invention remain as described in precedingsections. However, the articulating mechanism 1034 is altered to bereleasable. The tab 1032 is preformed or biased (as a result of itsspringy material and/or angle of deployment) not to lockably engage theindividual stops 1030. Instead, a moveable slider 1080 and retainerplate 1090 are positioned over the tab 1032 to deflect the tab downwardinto the individual stops. The shape of tab 1032 which is deflectedagainst the rib 1022 by the slider 1080 and retainer plate 1090 provideslocking of rib 1022 against one direction of travel (collapse) whileallowing travel in the opposite direction (expansion). The slider 1080has a wide area 1082 that provides the structural interference to flextab 1032 into the locking position. When the wide region 1082 ispositioned between retainer 1090 and tab 1032 the tab is forced againstthe slideably engaged rib 1022 and into the passing stops 1030 as therib slides through the articulating mechanism. The slider 1080 also hasa narrow region 1084 that will permit tab 1032 to relax and pull out ofthe stop 1030. By pulling the slider 1080 outward from the perpendicularplane of the ribs 1020 the narrow region 1084 is repositioned over thetab 1032, thereby allowing the tab to disengage from the stop 1030 andspring back upward against the retainer plate 1090.

With reference to FIG. 13B there is illustrated a partial view of amodule having one-rib and two-rib radial elements and releasablearticulating mechanisms 1034. The releasable articulating mechanisms onthe one-rib radial element are shown engaging the two ribs from theadjacent two-rib radial element. The slider may be modified on thisreleasable articulating mechanism to have two narrow regions forreleasing both tabs by pulling the one side of the slider.

Stent Manufacture

Preferred materials for the making the stents of the present inventioninclude 316 stainless steel, tantalum, titanium, tungsten, gold,platium, iridium, rhodium and alloys thereof. Also shape memory alloyssuch as Nitinol may be used in accordance with the present invention.Preferably, sheets are work-hardened prior to forming of the individualstent elements to increase strength. Methods of work hardening are wellknown in the art. Sheets are rolled under tension, annealed under heatand then re-worked. This may be continued until the desired modulus ofhardness is obtained. Most stents in commercial use today employ 0% to10% work hardened material in order to allow for “softer” material todeform to a larger diameter. In contrast, because expansion of thesliding and locking radial elements in accordance with the presentinvention depends on sliding rather than material deformation, it ispreferred to use harder materials, preferably in the range of about25-95% work hardened material to allow for thinner stent thickness. Morepreferably, the stent materials are 50-90% work hardened and mostpreferably, the materials are 80-85% work hardened.

Preferred methods of forming the individual elements from the metalsheets may be laser cutting, laser ablation, die-cutting, chemicaletching, plasma etching or other methods known in the art which arecapable of producing high-resolution components. The method ofmanufacture, in some embodiments, depends on the material used to formthe stent. Chemical etching provides high-resolution components atrelatively low price, particularly in comparison to high cost ofcompetitive product laser cutting. Tack-welding, adhesives, mechanicalattachment (snap-together), and other art-recognized methods ofattachment, may be used to fasten the individual elements. Some methodsallow for different front and back etch artwork, which could result inchamfered edges, which may be desirable to help improve engagements oflockouts.

In one preferred mode of the present invention, the stent is made, atleast in part, from a polymeric material, which may be degradable. Themotivation for using a degradable stent is that the mechanical supportof a stent may only be necessary for several weeks after angioplasty,particularly if it also controls restenosis and thrombosis by deliveringpharmacologic agents. Degradable polymeric stent materials are wellsuited for drug delivery.

It is believed that there is a need for short-term intervention sincethe majority of cardiac events occur in the first 6 months, includingin-stent restenosis. The permanency of metal stents presents long-termrisks and complications. With long lesions and full coverage, metalstents can also preclude surgical re-intervention. The ideal implant:(1) mimics the tissue it is designed to replace in size, shape, andmaterial consistency; (2) neither is disposed to infection nor evokes aforeign body response; (3) is a temporary prosthesis that takes oncharacteristics of the natural tissue as it disappears; and (4) is abiocompatible implant that has a smooth surface to minimize the risk forthrombus formation and macrophage enzyme activity.

Degradable stents have the potential to perform more like an idealimplant. Degradable stents that integrate seamlessly with the livinghost tissue may improve tissue biocompatibility due to their temporaryresidence. With the initial strength to secure the diseased tissue, suchstents may eliminate the concern for product migration over time andlong-term product failure. They may also minimize time, costs, andcomplications associated with re-intervention of specific andneighboring sites. Degradable stents have a clear advantage over metalstents in that they can dose the diseased tissue with a drug; comparedto drug coated metal stents, degradable stents can dose the tissue overa longer period of time.

Unlike restenosis after angioplasty, in-stent restenosis is aconsequence almost entirely of tissue hyperplasia, occurring principallyat the points where the stent's struts impinge upon the artery wall.Placement of an excessively stiff stent against the compliant vesselcreates a mismatch in mechanical behavior that results in continuouslateral expansile stress on the arterial wall. This stress can promotethrombosis, arterial wall thinning, or excessive cellular proliferation.Hence, polymeric biomaterials, which are more flexible, may minimize thepathology and are more likely to approximate the mechanical profile ofthe native tissue.

The intact internal elastic lamina (IEL) of a healthy artery serves asan effective barrier to (1) protect the underlying smooth muscle cells(SMC) from exposure to mitogens that induce hyperplasia, and (2) preventexposure to monocytes or lipid-filled macrophages and circulatingelastin peptides that promote hard plaque formation and narrowing of theartery. A biomaterial stent may minimize progression of disease statesby mimicking the barrier functions of the IEL: (1) by delivering acell-cycle inhibitor to counteract the affects of mitogens, and (2) byserving as a temporary physical barrier to the trafficking immune cells.

In the natural disease states, arteriostenosis and atherosclerosis,arteries can have a compromised or structurally discontinuous IEL. Thecause of the discontinuity is largely unknown. Elastases, circulatingelastin peptides, and elastin receptors may play a pivotal role alongwith denudation of the endothelium. A biomaterial stent that does notgrossly over expand the vessel wall may minimize the risk for furtherperforation of the IEL. In addition the stent surface can serve as ananchorage site for formation of an endothelial lining, the gatekeeper toblood elements and circulating molecules.

In one mode of the degradable stent of the present invention, the stentmatrix may be formulated so as to release a pharmacologic agent.Mechanical treatment of diseased vessels by angioplasty and stenting canfurther damage the arterial wall. Ironically, each of these practicescan promote thrombus formation and restenosis associated withreocclusion within 6- to 24-months post-operatively. These inadequateclinical outcomes are the impetus for development of many counteractivetherapies. Some new treatments for restenosis are use of radioisotopes,Paclitaxel and Rapamycin all of which inhibit vascular cellproliferation.

It is estimated that pharmacological interventions for restenosis needto occur continuously for 2-4 weeks following angioplasty or stentimplantation. It is also estimated that a polymer stent can deliver adrug dose that is ten times higher than systemic delivery. If a cellcycle inhibitor was released from a degradable stent, we may achieveoptimal long-term patency in the diseased vessel.

Degradable biomaterial stents may improve the long-term product safetyand efficacy for the patients. We believe that a completely degradable,drug-eluting stent that resides in the vessel for several weeks afterdeployment will be effective in controlling restenosis. Accordingly, thepresent invention encompasses stents having the sliding and lockinggeometry described above, wherein the stent components are made from afunctional biomaterial.

The mechanical properties of the degradable biomaterial are selected inaccordance with the present invention to exhibit at least one, andpreferably more, of the following characteristics: (1) resist failuredue to the multiaxial stress-strain behavior of native arteries andexceeds that of annealed metals, which are known to fail for stentapplications; (2) retain mechanical strength during several weeks ormonths post-deployment; (3) degrade via hydrolytic or enzymaticdegradation preferably with surface erosion whereby the implant degradesuniformly and maintains its original shape as it degrades; (4) maintainsfavorable hemodynamics; (5) exhibits a hydrophilic, negatively charged,smooth and uniform surface with a low critical surface tension; (6)supports endothelialization; (7) is nontoxic and eliminated from thebody safely, i.e., no systemic effects; and (8) includes ananti-restenosis pharmacological agent. The pharmacologic agent may be acell-cycle inhibitor that inhibits SMC proliferation, allows forfavorable early and late remodeling, and that is stable in thebiomaterial. The degradable biomaterial and pharmacologic agentpreferably provide dosing of the lesion for about three to four weeks orthrough the degradation cycle of stent.

Degradable plastic or natural (animal, plant or microbial) orrecombinant materials in accordance with one aspect of the presentinvention may include polydepsipeptides, nylon copolymides, conventionalpoly(amino acid) synthetic polymers, pseudo-poly(amino acids), aliphaticpolyesters, such as polyglycolic acid (PGA), polylactic acid (PLA),polyalkylene succinates, polyhydroxybutyrate (PHB), polybutylenediglycolate, and poly epsilon-caprolactone (PCL), polydihydropyrans,polyphosphazenes, polyorthoesters, polycyanoacrylates, polyanhydrides,polyketals, polyacetals, poly(α-hydroxy-esters), poly(carbonates),poly(imino-carbonates), poly(β-hydroxy-esters), polypeptides, and theirchemical modifications and combinations (blends and copolymers) and manyother degradable materials known in the art. (See e.g., Atala, A.,Mooney, D. Synthetic Biodegradable Polymer Scaffolds. 1997 Birkhauser,Boston; incorporated herein by reference).

In one preferred mode, the degradable materials are selected from thegroup consisting of poly(alkylene oxalates), polyalkanotes, polyamides,polyaspartimic acid, polyglutarunic acid polymer, poly-p-diaxanone(e.g., PDS from Ethicon), polyphosphazene, and polyurethane.

In a more preferred mode, the degradable materials are selected from thegroup consisting of poly(glycolide-trimethylene carbonate); terpolymer(copolymers of glycolide, lactide or dimethyltrimethylene carbonate);polyhydroxyalkanoates (PHA); polyhydroxybutyrate (PHB) andpoly(hydroxybutyrate-co-valerate) (PHB-co-HV) and copolymer of same;poly(epsilon-caprolactone) and copolymers (e.g., lactide or glycolide);poly(epsilon-caprolactone-dimethyltrimethylene carbonate); polyglycolicacid (PGA); and poly-L and poly-D(lactic acid) and copolymers andadditives (e.g., calcium phosphate glass) and lactic acid/ethyleneglycol copolymers.

In a most preferred mode, the degradable materials are selected from thegroup consisting of polyarylates (L-tyrosine-derived) or free acidpolyarylates, polycarbonates (L-tyrosine-derived), poly(ester-amides),poly(propylene fumarate-co-ethylene glycol) copolymer (i.e., fumarateanhydrides), polyanhydride esters (mechanically stronger) andpolyanhydrides (mechanically weaker), polyorthoesters, ProLastin orsilk-elastin polymers (SELP), calcium phosphate (BIOGLASS), magnesiumalloys, and a composition of PLA, PCL, PGA ester commercial polymersused sigularly or in any mixture.

Natural polymers (biopolymers) include any protein or peptide. These canbe used in a blend or copolymer with any of the other aforementioneddegradable materials, as well as with pharmacologic substances, or withhydrogels, or alone. Typically, these biopolymers degrade upon theaction of enzymes. Preferred biopolymers may be selected from the groupconsisting of aliginate, cellulose and ester, chitosan (NOCC andNOOC-G), collagen, cotton, dextran, elastin, fibrin, gelatin, hyaluronicacid, hydroxyapatite, spider silk, other polypeptides and proteins, andany combinations thereof.

Coatings for degradable and metal stent materials may be selected fromthe group consisting of hydrogels, such as: NO-carboxymethyl chitosan(NOCC), PEG diacrylate with drug (intimal layer) with second layerwithout drug (blood flow contact), polyethylene oxide, polyvinylalcohol(PVA), PE-oxide, polyvinylpyrolidone (PVP), polyglutarunic acidpolymers, DMSO or alcohols and any combinations thereof.

Where plastic and/or degradable materials are used, the elements may bemade using hot-stamp embossing to generate the parts and heat-staking toattach the linkage elements and coupling arms. Other preferred methodscomprise laser ablation using a screen, stencil or mask; solventcasting; forming by stamping, embossing, compression molding,centripital spin casting and molding; extrusion and cutting,three-dimensional rapid prototyping using solid free-form fabricationtechnology, stereolithography, selective laser sintering, or the like;etching techniques comprising plasma etching; textile manufacturingmethods comprising felting, knitting, or weaving; molding techniquescomprising fused deposition modeling, injection molding, roomtemperature vulcanized (RTV) molding, or silicone rubber molding;casting techniques comprising casting with solvents, direct shellproduction casting, investment casting, pressure die casting, resininjection, resin processing electroforming, or reaction injectionmolding (RIM). These parts may be connected or attached by solvent orthermal bonding, or by mechanical attachment. Preferred methods ofbonding comprise the use of ultrasonic radiofrequency or other thermalmethods, and by solvents or adhesives or ultraviolet curing processes orphotoreactive processes. The elements may be rolled by thermal forming,cold forming, solvent weakening forming and evaporation, or bypreforming parts before linking. Soluble materials such as hydrogelswhich are hydrolized by water in blood could also be used, for example,cross-linked poly 2-hydroxyethyl methacrylate (PHEMA) and itscopolymers, e.g., polyacrylamide, and polyvinyl alcohol.

The addition of radiopacifiers (i.e., radiopaque materials) tofacilitate tracking and positioning of the stent could be added in anyfabrication method or absorbed into or sprayed onto the surface of partor all of the implant. The degree of radiopacity contrast can be alteredby implant content. Radiopacity may be imparted by covalently bindingiodine to the polymer monomeric building blocks of the elements of theimplant. Common radiopaque materials include barium sulfate, bismuthsubcarbonate, and zirconium dioxide. Other radiopaque elements include:cadmium, tungsten, gold, tantalum, bismuth, platium, iridium, andrhodium. In one preferred embodiment, iodine may be employed for itsradiopacity and antimicrobial properties. Radiopacity is typicallydetermined by fluoroscope or x-ray film.

The stents in accordance with the present invention, may also be usefulin vessel grafts, wherein the stent is covered with a sheath formed fromeither a polymeric material, such as expanded PTFE, degradable polymers,or a natural material, such as fibrin, pericardial tissue, or theirderivatives, as will be known to those of skill in the art. The coveringmay be attached to the inner or outer surface of the stent.Alternatively, the stent may be embedded within layers of the coveringmaterial.

Once the stent components have been cut out and assembled into flatmodules (see plan views described with respect to FIGS. 1, 2, 4-8, and11), and linkage elements between adjacent modules have been connected(e.g., by welding, inter-weaving frame elements, etc.), the flat sheetsof material are rolled to form a tubular member. Coupling arms fromfloating coupling elements and end portions are joined (e.g., bywelding) to maintain the tubular shape. In embodiments that do notinclude coupling elements, the end portions of the top and bottom radialelements in a module may be joined. Alternatively, where sliding isdesired throughout the entire circumference, a sliding and lockingarticulation can be made between the end portion of the top radialelement and the rib(s) of the bottom radial element (e.g., bytack-welding, heat-staking or snap-together). Similarly, a correspondingarticulation can be made between the end portion of the bottom radialelement and the rib(s) of the top radial element.

Rolling of the module(s) to form a tubular member can be accomplished byany means known in the art, including rolling between two plates, whichare each padded on the side in contact with the stent elements. Oneplate is held immobile and the other can move laterally with respect tothe other. Thus, the stent elements sandwiched between the plates may berolled about a mandrel by the movement of the plates relative to oneanother. Alternatively, 3-way spindle methods known in the art may alsobe used to roll the tubular member. Other rolling methods that may beused in accordance with the present invention include those used for“jelly-roll” designs, as disclosed for example, in U.S. Pat. Nos.5,421,955, 5,441,515, 5,618,299, 5,443,500, 5,649,977, 5,643,314 and5,735,872; the disclosures of which are incorporated herein in theirentireties by reference thereto.

The construction of the stent in this fashion provides a great deal ofbenefit over the prior art. The construction of the locking mechanism islargely material-independent. This allows the structure of the stent tocomprise high strength materials, not possible with designs that requiredeformation of the material to complete the locking mechanism. Theincorporation of these materials will allow the thickness required ofthe material to decrease, while retaining the strength characteristicsof thicker stents. In preferred embodiments, the frequency of lockingholes or stops present on selected circumferential ribs preventsunnecessary recoil of the stent subsequent to expansion.

Drugs Incorporated into Stents

Drugs and other bioactive compounds can be incorporated into thedegradable matrices themselves or coated on the non-degradable stentmaterials, thereby providing sustained release of such compounds at thesite of the stent. In addition, degradable biomaterial can be fabricatedin a various forms and processed into the stent components. Preferredbiomaterials would incorporate a pharmaceutical agent blended with thedegradable polymer prior to fabricating the stent. The preferredpharmaceutical agent(s) control restenosis (including neointimalthickening, intimal hyperplasia and in-stent restenosis or limitsvascular smooth muscle cell overgrowth in the lumen of a stented vessel.Other body applications may require different drugs.

In a another aspect of the present invention, the stent biomaterial mayalso incorporate a hydrogel that acts to prevent adhesions of bloodcells, extracellular matrix or other cell types. For instance, NOCC andNOCC-G chitosan. In another aspect, the pharmaceutical agents orhydrogels can be coated onto the surface of the biomaterial singularlyor in mixtures or in combination with other binders required to adhereor absorb the pharmaceutical or hydrogel to the biomaterial surface. Inaddition or in the alternative, the pharmaceutical or hydrogel orgenetic material may be incorporated with the biomaterial polymer,microspheres, or hydrogel.

Use of synthetic, natural (plant, microbial, viral or animal-derived)and recombinant forms having selected functions or chemical propertiescan be mixed with complementary substances (e.g., anti-thrombotic andanti-restenosis substances; nucleic acids and lipid complexes).Pharmacologic agents may also incorporate use of vitamins or minerals.For instance, those that function directly or indirectly throughinteractions or mechanisms involving amino acids, nucleic acids (DNA,RNA), proteins or peptides (e.g., RGD peptides), carbohydrate moieties,polysaccharides, liposomes, or other cellular components or organellesfor instance receptors and ligands.

Pharmaceutical agents may be polar or possess a net negative or positiveor neutral charge; they may be hydrophobic, hydrophilic or zwitterionicor have a great affinity for water. Release may occur by controlledrelease mechanisms, diffusion, interaction with another agent(s)delivered by intravenous injection, aerosolization, or orally. Releasemay also occur by application of a magnetic field, an electrical field,or use of ultrasound.

The variety of compounds which may be used for coating metallic stentsor for incorporating into degradable stent materials have been disclosedby Tanguay et al. Cardio Clin (1994) and Nikol et al. Atherosclerosis(1996); these references are herein incorporated in their entirety byreference thereto. These compounds include antiplatelet agents (Table1), antithrombin agents (Table 2), and antiproliferative agents (Table3). Some preferred agents that fall within these classes of compoundsare presented in Tables 1-3 (below). TABLE 1 Antiplatelet AgentsCompound Action Aspirin Cyclo-oxygenase inhibition DipyridamolePhosphodiesterase inhibition Ticlopidine Blocks interaction betweenplatelet receptors, fibrinogen, and von Willebrand factors C7E3Monoclonal antibody to the glycoprotein IIb/IIIa receptor IntegrelinCompetitive glycoprotein Iib/IIIa receptor inhibition MK-852,Glycoprotein IIb/IIIa receptor inhibition MK-383 RO-44-9883 GlycoproteinIIb/IIIa receptor inhibition

TABLE 2 Antithrombin Agents Compound Action Heparin Antithrombin IIIcofactor Low molecular weight Inhibition of factor Xa by antithrombinIII heparin (LMWH) R-Hirudin Selective thrombin inhibition HirulogSynthetic direct thrombin inhibition Argatroban, efegatran Syntheticcompetitive thrombin inhibition Tick anticoagulant Specific thrombininhibition peptide Ppack Irreversible thrombin inhibition

Additional anti-thrombogenic substances and formulations includeendothelium-derived relaxing factor, prostaglandin I₂, plasminogenactivator inhibitor, tissue-type plasminogen activator (tPA), ReoPro:anti-platelet glycoprotein Ib/IIIa integrin receptor, heparin, polyamineto which dextran sulfate and heparin are covalently bonded,heparin-containing polymer coating for indwelling implants (MEDI-COAT bySTS Biopolymers), polyurethaneurea/heparin, hirudin/prostacyclin andanalogues, fibrin and fibrin peptide A, lipid-lowering drugs, e.g.,Omega-3 fatty acids, and chrysalin (aka TRAP-508) by Chrysalis VascularTechnologies (which is a synthetically manufactured peptide portion ofthe human enzyme thrombin, responsible for blood clotting and initiatingcellular/tissue repair). Chrysalin mimics specific attributes ofthrombin by interacting with receptors on cells involved in tissuerepair.

Other anti-restenosis substances in accordance with the presentinvention include INTEGRILIN® (eptifibatide) by COR Therapeutics (blocksplatelet clumping), Resten-NG (NeuGene) by AVI BioPharma (syntheticversion of C-MYC oncogene), and Implant Sciences Corp., BiodivYsio(phosphorylcholine (PC)) by Abbott Laboratories Inc. and BiocompatiblesInternational PLC, Liposomal Prostaglandin El by Endovasc Ltd. andCollaborative BioAlliance, Adenovirus vectors to carry genes to vascularsmooth muscle cells (Boston Scientific Corp and CardioGene TherapeuticsInc.), TAXOL (paclitaxel) by Bristol-Myers Squibb (prevents celldivision by promoting the assembly of and inhibiting the disassembly ofmicrotubules), and Raparnycin or nitric oxide. Other drugs includeceramide, tranilast, probucol, statins, cilostazol, and low molecularweight variations of heparin.

A variety of compounds are considered to be useful in controllingvascular restenosis and in-stent restenosis. Some of these preferredantiproliferative agents are presented in Table 3 (below). TABLE 3Antiproliferative Agents Compound Action Angiopeptin Somatostatin analogwhich inhibits IGF-I Ciprostene Prostacyclin analog Calcium Inhibitionof slow calcium channels blockers Colchicine Antiproliferative andmigration inhibition Cyclosporine Immunosuppressive, intracellulargrowth signal inhibition Cytorabine Antineoplastic, DNA synthesisinhibition Fusion proteins Toxin-bounded growth factor LioprostProstacyclin analog Ketaserine Serotonin antagonist Prednisone Steroidhormone Trapidil Platelet-derived growth factor inhibitor (inhibitor ofthromboxane-A2 and/or PDGF receptor antagonist)

Specific therapeutic agents have also been identified which may modulatesmooth muscle cell (SMC) proliferation. Since SMC cell proliferation hasbeen implicated in atherosclerotic stenosis as well as post-operativerestenosis, incorporation of such agents may be particularly useful.These include without limitation, regulators of SMC mitosis (e.g.,TAXOL, Rapamycin, or ceramide) and stimulators and triggers forextracellular matrix production, such as anti-FGF and TGF-β₁ strategies,tissue inhibitor metalloproteinases (TIMPs), and matrixmetaloproteinases (MMPs).

Various compounds address specific pathologic events and/or vasculardiseases. Some of these therapeutic target compounds are summarized inTable 4 (below). TABLE 4 Specific Therapeutic Target CompoundsPathologic Event Therapeutic Target Endothelial dysfunction Nitric oxideinducer or antioxidants Endothelial injury Administer VEGF; FGF's Cellactivation & MEF-2 & Gax modulators; NFKB antagonists; phenotypicmodulation cell cycle inhibitors Dysregulated cell growth E2F decoys; RBmutants; cell cycle inhibitors Dysregulated apoptosis Bax or CPP32inducers; Bcl-2 inhibitors; integrin antagonists Thrombosis IIb/IIIablockers; tissue factor inhibitors; antithrombin agents Plaque ruptureMetalloproteinase inhibitors; leukocyte adhesion blockers Abnormal cellmigration Integrin antagonists: PDGF blockers; plasminogen activatorinhibitors Matrix modification Metalloproteinase inhibitors, plasminogenantagonists; matrix protein cross-linking modifiers

The therapeutic agents to be bonded to or incorporated within the stentmaterials of the present invention may be classified in terms of theirsites of action in the host. The following agents are believed to exerttheir actions extracellularly or at specific membrane receptor sites.These include corticoids and other ion channel blockers, growth factors,antibodies, receptor blockers, fusion toxins, extracellular matrixproteins, peptides, or other biomolecules (e.g., hormones, lipids,matrix metalloproteinases, and the like), radiation, anti-inflammatoryagents including cytokines such as interleukin-1 (IL-1), and tumornecrosis factor alpha (TNF-α), gamma interferon (interferon-γ), andTranilast, which modulate the inflammatory response.

Other groups of agents exert their effects at the plasma membrane. Theseinclude those involved in the signal transduction cascade, such ascoupling proteins, membrane associated and cytoplasmic protein kinasesand effectors, tyrosine kinases, growth factor receptors, and adhesionmolecules (selectins and integrins).

Some compounds are active within the cytoplasm, including for example,heparin, ribozymes, cytoxins, antisense oligonucleotides, and expressionvectors. Other therapeutic approaches are directed at the nucleus. Theseinclude gene integration, proto-oncogenes, particularly those importantfor cell division, nuclear proteins, cell cycle genes, and transcriptionfactors.

Genetic approaches to control restenosis include without limitation: useof antisense oligonucleotides to PDGFR-ββ mRNA to control PDGFexpression; use of antisense oligonucleotides for nuclear antigens c-mybor c-myc oncogenes (Bauters et al., 1997, Trends CV Med); use ofantisense phosphorothioate oligodeoxynucleotides (ODN) against cdk 2kinase (cyclin dependent kinase) to control the cell cycle of vascularSMC (Morishita et al, 1993, Hypertension); use of VEGF gene (or VEGFitself) to stimulate reconstructive wound healing such asendothelialization and decrease neointima growth (Asahara et al 1995);delivery of the nitric oxide synthetase gene (eNOS) to reduce vascularSMC proliferation (Von Der Leyen et al., 1995, Proc Natl Acad Sci); useof adenovirus expressing plasminogen activator inhibitor-1 (PAI-1) toreduce vascular SMC migration and thereby diminish restenosis (Carmelietet al., 1997, Circulation); stimulation of apolipoprotein A-1 (ApoA1)over-expression to rebalance serum levels of LDL and HDL; use ofapoptosis gene products to promote cell death (of SMC) and cytotacticgene products to that regulate cell division (tumor suppressor proteinp53 and Gax homeobox gene product to suppress ras; p21 over expression);and inhibition of NFKB activation (e.g., p65) to control SMCproliferation (Autieri et al., 1994, Biochem Biophys Res Commun).

Other therapeutic substances that may be useful as stent coatings and/ordepot formulations incorporated within degradable stents include:antibodies to ICAM-1 for inhibition of monocyte chemotactic recruitmentand adhesion, macrophage adhesion and associated events (Yasukawa et al,1996, Circulation); toxin based therapies such as chimeric toxins orsingle toxins to control vascular SMC proliferation (Epstein et al.,1991, Circulation); bFGF-saporin to selectively stop SMC proliferationamong those cells with a large number of FGF-2 receptors (Chen et al,1995, Circulation), suramin inhibits migration and proliferation byblocking PDGF-induced and/or mitogen activated protein kinase(MAPK-AP-1)-induced signaling (Hu et al., Circulation, 1999); BeraprostSodium, a chemically stable prostacyclin analogue (PG I₂), suppressesintimal thickening and lumenal narrowing of coronary arteries. (Kurisuet al, Hiroshima J. Med Sci, 1997); Verapamil inhibits neointimal smoothmuscle cell proliferation (Brauner et al., J Thorac Cardiovasc Surg1997), agents that block the CD154 or CD40 receptor may limit theprogression of atherosclerosis (E Lutgens et al., Nature Medicine 1999),agents that control responses of shear stress response elements ormechanical stress or strain elements or heat shock genes; andanti-chemoattractants for SMC and inflammatory cells.

In addition or in the alternative, cells could be encapsulated in adegradable microsphere, or mixed directly with polymer, or hydrogel andserve as vehicle for pharmaceutical delivery. Living cells could be usedto continuously deliver pharmaceutical type molecules, for instance,cytokines and growth factors. Nonliving cells could also serve as alimited or timed release system. Cells or any origin may be used inaccordance with this aspect of the present invention. Further, preservedor dehydrated cells which retain their viability when rehydrated may beused. Native, chemically modified (processed), and/or geneticallyengineered cells may be used.

Stent Deployment

Stents can be deployed in a body lumen by means appropriate to theirdesign. One such method would be to fit the collapsed stent over aninflatable element of a balloon catheter and expand the balloon to forcethe stent into contact with the body lumen. As the balloon is inflated,the problem material in the vessel is compressed in a directiongenerally perpendicular to the wall of the vessel which, consequently,dilates the vessel to facilitate blood flow therethrough. Radialexpansion of the coronary artery occurs in several different dimensionsand is related to the nature of the plaque. Soft, fatty plaque depositsare flattened by the balloon and hardened deposits are cracked and splitto enlarge the lumen. It is desirable to have the stent radially expandin a uniform manner.

Alternatively, the stent may be mounted onto a catheter that holds thestent as it is delivered through the body lumen and then releases thestent and allows it to self-expand into contact with the body lumen.This deployment is effected after the stent has been introducedpercutaneously, transported transluminally and positioned at a desiredlocation by means of the catheter. The retaining means may comprise aremovable sheath.

The popular stents in use today are stiffer than desired. Their relativeflexibility is shown in FIGS. 14A and 14B. The flexibility ofundeployed/mounted stents is shown in FIG. 14A. All deflection testswere conducted in saline at body temperature as defined in the ASTMstandards for stent measurements. The S540 (2.5×18 mm) and S670 (3.0×18mm) stents are produced by Medtronic, the TRISTAR® (2.5×18 mm) is madeby Guidant, VELOCITY (2.5×13 mm) is produced by J&J, and the Nir (2.5×32mm) is marketed by Boston Scientific. The results shown in FIG. 14A(undeployed on a delivery catheter) indicate that the other stentstested are more than 2-fold stiffer than the stent (MD3) made inaccordance with the present invention. The difference in flexibility ofthe deployed (expanded) stents is even more pronounced, as illustratedin FIG. 14B.

Because of the very low profile, small collapsed diameter and greatflexibility, stents made in accordance with the present invention may beable to navigate small or torturous paths. Thus, the low-profile stentof the present invention may be useful in coronary arteries, carotidarteries, vascular aneurysms (when covered with a sheath), andperipheral arteries and veins (e.g., renal, iliac, femoral, popliteal,sublavian, aorta, intercranial, etc.). Other nonvascular applicationsinclude gastrointestinal, duodenum, biliary ducts, esophagus, urethra,reproductive tracts, trachea, and repiratory (e.g., bronchial) ducts.These applications may or may not require a sheath covering the stent.

The stents of the present invention are adapted for deployment usingconventional methods known in the art and employing percutaneoustransluminal catheter devices. The stents are designed for deployment byany of a variety of in situ expansion means, such as an inflatableballoon or a polymeric plug that expands upon application of pressure.For example, the tubular body of the stent is first positioned tosurround a portion of an inflatable balloon catheter. The stent, withthe balloon catheter inside is configured at a first, collapseddiameter. The stent and the inflatable balloon are percutaneouslyintroduced into a body lumen, following a previously positionedguidewire in an over-the-wire angioplasty catheter system, and trackedby a fluoroscope, until the balloon portion and associated stent arepositioned within the body passageway at the point where the stent is tobe placed. Thereafter, the balloon is inflated and the stent is expandedby the balloon portion from the collapsed diameter to a second expandeddiameter. After the stent has been expanded to the desired finalexpanded diameter, the balloon is deflated and the catheter iswithdrawn, leaving the stent in place. The stent may be covered by aremovable sheath during delivery to protect both the stent and thevessels.

The expanded diameter is variable and determined by the desired expandedinternal diameter of the body passageway. Accordingly, the controlledexpansion of the stent is not likely to cause a rupture of the bodypassageway. Furthermore, the stent will resist recoil because thelocking means resist sliding of the elongated ribs within thearticulating mechanism on the end portions of the radial elements. Thus,the expanded intraluminal stent will continue to exert radial pressureoutward against the wall of the body passageway and will therefore, notmigrate away from the desired location.

While a number of preferred embodiments of the invention and variationsthereof have been described in detail, other modifications and methodsof using and medical applications for the same will be apparent to thoseof skill in the art. Accordingly, it should be understood that variousapplications, modifications, and substitutions may be made ofequivalents without departing from the spirit of the invention or thescope of the claims.

1. An expandable stent, comprising: a tubular member having acircumference which is adjustable between at least a first collapseddiameter and at least a second expanded diameter, said tubular membercomprising: at least two slidably engaged radial elements, wherein eachradial element defines a portion of the circumference of the tubularmember, and comprises a tab, a locking slot which comprises a stoptherein and defines a travel path, and an entry slot configured to allowa tab to fit into and slidably engage the locking slot, wherein the stopis configured to permit one-way sliding of the tab along the travelpath, such that said tubular member can expand from the first collapseddiameter to the second expanded diameter with reduced recoil as theslidably engaged radial elements slide apart from one another.
 2. Theslide-and-lock stent of claim 1, wherein no radial element overlaps withitself in the expanded diameter.
 3. The slide-and-lock stent of claim 1,wherein the travel path is aligned substantially with the circumference.4. The slide-and-lock stent of claim 1, wherein the locking slot furthercomprises a plurality of stops which are disposed along both proximaland distal sides of the slot.
 5. The slide-and-lock stent of claim 4,wherein the plurality of stops are substantially evenly distributed onthe proximal and distal sides of the slot.
 6. The slide-and-lock stentof claim 5, wherein the stops on the proximal side are circumferentiallyoffset from the stops on the distal side, such that the travel pathdefines a zig-zag pattern.
 7. The slide-and-lock stent of claim 1,wherein at least one radial element further comprises a frame element.8. The slide-and-lock stent of claim 7, wherein the frame elementfurther comprises a linkage element for connecting to a longitudinallyadjacent radial element.
 9. The slide-and-lock stent of claim 1, whereinthe radial elements further comprise at least one elongated rib.
 10. Theslide-and-lock stent of claim 9, wherein the locking slot is disposedalong a portion of the elongated rib.
 11. The slide-and-lock stent ofclaim 1, wherein the radial elements further comprise end portions. 12.The slide-and-lock stent of claim 1, wherein no components have beenwelded.
 13. The slide-and-lock stent of claim 1, wherein the stentfurther comprises a bioactive agent.
 14. The slide-and-lock stent ofclaim 13, wherein the bioactive agent is selected from the groupconsisting of antiplatelet agents, antithrombin agents,antiproliferative agents and antiinflamitory agents.